title: Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q(+) pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Sawai
authors.forename: Vanja
authors.initials: V
authors.lastname: Sisirak
authors.forename: Hiyaa S
authors.initials: HS
authors.lastname: Ghosh
authors.forename: Esther Z
authors.initials: EZ
authors.lastname: Hou
authors.forename: Michele
authors.initials: M
authors.lastname: Ceribelli
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002465:Cell Movement; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C527089:Klra17 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; D019713:Receptors, CCR5; C493716:Runx2 protein, mouse; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors